Viral Diversity in Some Immunodominant Epitopes: Possible Implications for Retroviral Immunopathogenesis (original) (raw)

HIV infection en route to endogenization: two cases

Clinical Microbiology and Infection, 2015

The long-term spontaneous evolution of humans and the human immunodeficiency virus (HIV) is not well characterized; many vertebrate species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV. We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses. We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3-100% per gene) and 24% overall (0-50% per gene)). In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection. We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection. Furthermore, we propose that a cure for HIV may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells, which defines viral eradication.

MOLECULAR BIOLOGY OF HUMAN IMMUNODEFICIENCY VIRUSES: HIV-l AND HIV-2

The Medical Journal of The Islamic Republic of Iran, 1997

Since the emergence of the acquired immunodeficiency syndrome (AIDS) and discovery of its etiological agents, human immunodeficiency viruses type 1 and type 2 (mV1 and mv -2), much new information on the epidemiology, pathology and basic biology of these viruses has been discovered. This review will focus on some of the highlights in the field of HIV from the perspective of basic molecular virology to some of the recent issues in clinical studies in the past and present, and by no means reflects the �oluminous information and research data gathered worldWIde on HIV / AIDS. Current complexities in mv pathogenesis are still responsible for the lack of an effective cure or vaccine to control the spread of the virus. Most notably, the genetic heterogeneity and mechanisms of molecular pathogenesis of the virus have been the counteracting force behind the unceasing efforts to obtain an effective therapy or vaccine.

Selection on the Human Immunodeficiency Virus Type 1 Proteome following Primary Infection

Journal of Virology, 2006

Typically during human immunodeficiency virus type 1 (HIV-1) infection, a nearly homogeneous viral population first emerges and then diversifies over time due to selective forces that are poorly understood. To identify these forces, we conducted an intensive longitudinal study of viral genetic changes and T-cell immunity in one subject at <17 time points during his first 3 years of infection, and in his infecting partner near the time of transmission. Autologous peptides covering amino acid sites inferred to be under positive selection were powerful for identifying HIV-1-specific cytotoxic-T-lymphocyte (CTL) epitopes. Positive selection and mutations resulting in escape from CTLs occurred across the viral proteome. We detected 25 CTL epitopes, including 14 previously unreported. Seven new epitopes mapped to the viral Env protein, emphasizing Env as a major target of CTLs. One-third of the selected sites were associated with epitopic mutational escapes from CTLs. Most of these resulted from replacement with amino acids found at low database frequency. Another one-third represented acquisition of amino acids found at high database frequency, suggesting potential reversions of CTL epitopic sites recognized by the immune system of the transmitting partner and mutation toward improved viral fitness in the absence of immune targeting within the recipient. A majority of the remaining selected sites occurred in the envelope protein and may have been subjected to humoral immune selection. Hence, a majority of the amino acids undergoing selection in this subject appeared to result from fitness-balanced CTL selection, confirming CTLs as a dominant selective force in HIV-1 infection.